Histology-driven data mining of lipid signatures from multiple imaging mass spectrometry analyses: application to human colorectal cancer liver metastasis biopsies.

Imaging mass spectrometry (IMS) represents an innovative tool in the cancer research pipeline, which is increasingly being used in clinical and pharmaceutical applications. The unique properties of the technique, especially the amount of data generated, make the handling of data from multiple IMS acquisitions challenging. This work presents a histology-driven IMS approach aiming to identify discriminant lipid signatures from the simultaneous mining of IMS data sets from multiple samples. The feasibility of the developed workflow is evaluated on a set of three human colorectal cancer liver metastasis (CRCLM) tissue sections. Lipid IMS on tissue sections was performed using MALDI-TOF/TOF MS in both negative and positive ionization modes after 1,5-diaminonaphthalene matrix deposition by sublimation. The combination of both positive and negative acquisition results was performed during data mining to simplify the process and interrogate a larger lipidome into a single analysis. To reduce the complexity of the IMS data sets, a sub data set was generated by randomly selecting a fixed number of spectra from a histologically defined region of interest, resulting in a 10-fold data reduction. Principal component analysis confirmed that the molecular selectivity of the regions of interest is maintained after data reduction. Partial least-squares and heat map analyses demonstrated a selective signature of the CRCLM, revealing lipids that are significantly up- and down-regulated in the tumor region. This comprehensive approach is thus of interest for defining disease signatures directly from IMS data sets by the use of combinatory data mining, opening novel routes of investigation for addressing the demands of the clinical setting.

Nanopartícul·les core-shell estabilitzades en polímer amb propietats calítiques i bactericides medioambientalment segure

Aquest projecte de doctorat és un treball interdisciplinari adreçat a l’obtenció de nous nanocompòsits (NCs) funcionals sintetitzats a partir de materials polimèrics bescanviadors d’ions que són modificats amb nanopartícules metàl•liques (NPMs) de diferent composició. Els materials desenvolupats s’avaluen en funció de dues possibles aplicacions: 1) com a catalitzadors de reaccions orgàniques d’interès actual (NCs basats en pal•ladi) i, 2) la seva dedicació a aplicacions bactericides en el tractament d’aigües domèstiques o industrials (NCs basats en plata). El desenvolupament de nanomaterials és de gran interès a l’actualitat donades les seves especials propietats, l’aprofitament de les quals és la força impulsora per a la fabricació de nous NCs. Les nanopartícules metàl•liques estabilitzades en polímer (Polymer Stabilized Metal Nanoparticles, PSNPM) s’han preparat mitjançant la tècnica in-situ de síntesi intermatricial (Inter-matrix synthesis, IMS) que consisteix en la càrrega seqüencial dels grups funcionals de les matrius polimèriques amb ions metàl•lics, i la seva posterior reducció química dins de la matriu polimèrica de bescanvi iònic. L’estabilització en matrius polimèriques evita l’agregació entre elles (self-aggreagtion), un dels principals problemes coneguts de les NPs. Pel desenvolupament d’aquesta metodologia, s’han emprat diferents tipus de matrius polimèriques de bescanvi iònic: membrana Sulfonated PolyEtherEtherKetone, SPEEK, així com fibres sintètiques basades en polypropilè amb diferents tipus de grups funcionals, que ens permeten el seu ús com a filtres en la desinfecció de solucions aquoses o com a material catalitzador. Durant el projecte s’ha anat avançant en l’optimització del material nanocomposite final per a les aplicacions d’interès, en quant activitat i funcionalitat de les nanopartícules i estabilitat del nanocomposite. Així, s’ha optimitzat la síntesi de NPs estabilitzades en resines de bescanvi iònic, realitzant un screening de diferents tipus de resines i la seva avaluació en aplicacions industrials d’interès.

Development of a new tool for assessing health-related quality of life in patients with primary hyperparathyroidism.

BACKGROUND Several studies in recent years have evaluated Health Related Quality of Life (HRQoL) of patients with primary hyperparathyroidism (PHPT). No disease specific questionnaires are available to assess the impact of the disease. The aim of this research is to describe the development of a new disease specific Quality of Life (QoL) questionnaire for use specifically with PHPT patients. METHODS A conceptual model was developed describing the impact of the disease and its symptoms on QoL domains. A literature review was conducted to identify the most relevant domains. A focus group with experts was used to validate the domains; 24 patients were also interviewed to complement the information from the patient's perspective. A content analysis of the interviews was performed to identify items related with the impact of the disease, leading to PHPQoL-V.1 which was presented to a sample of 67 patients. Reliability was assessed by Cronbach's coefficient alpha and item-total score correlations. Validity was assessed by a factor analysis performed to determine the number of domains. Rasch analysis was carried out in order to refine the questionnaire items. RESULTS 259 items were extracted from the interviews that were subsequently reduced to 34 items. Cronbach's coefficient alpha was 0.92. The factor analysis extracted two domains (physical and emotional). After Rasch analysis the questionnaire PHPQoL-V.2 kept 16 items (9 physical and 7 emotional). The questionnaire was developed in a Spanish population and the final version was translated to English through translation and back-translation. CONCLUSION The first disease specific HRQoL questionnaire for PHPT patients (PHPQoL-16) has been developed. Validation studies designed to assess measurement properties of this tool are currently underway.

Modèle et application pour la génération automatique de parcours d'apprentissage personnalisés à partir de sources de confiance

Résumé Lors d'une recherche d'information, l'apprenant est très souvent confronté à des problèmes de guidage et de personnalisation. Ceux-ci sont d'autant plus importants que la recherche se fait dans un environnement ouvert tel que le Web. En effet, dans ce cas, il n'y a actuellement pas de contrôle de pertinence sur les ressources proposées pas plus que sur l'adéquation réelle aux besoins spécifiques de l'apprenant. A travers l'étude de l'état de l'art, nous avons constaté l'absence d'un modèle de référence qui traite des problématiques liées (i) d'une part aux ressources d'apprentissage notamment à l'hétérogénéité de la structure et de la description et à la protection en terme de droits d'auteur et (ii) d'autre part à l'apprenant en tant qu'utilisateur notamment l'acquisition des éléments le caractérisant et la stratégie d'adaptation à lui offrir. Notre objectif est de proposer un système adaptatif à base de ressources d'apprentissage issues d'un environnement à ouverture contrôlée. Celui-ci permet de générer automatiquement sans l'intervention d'un expert pédagogue un parcours d'apprentissage personnalisé à partir de ressources rendues disponibles par le biais de sources de confiance. L'originalité de notre travail réside dans la proposition d'un modèle de référence dit de Lausanne qui est basé sur ce que nous considérons comme étant les meilleures pratiques des communautés : (i) du Web en terme de moyens d'ouverture, (ii) de l'hypermédia adaptatif en terme de stratégie d'adaptation et (iii) de l'apprentissage à distance en terme de manipulation des ressources d'apprentissage. Dans notre modèle, la génération des parcours personnalisés se fait sur la base (i) de ressources d'apprentissage indexées et dont le degré de granularité en favorise le partage et la réutilisation. Les sources de confiance utilisées en garantissent l'utilité et la qualité. (ii) de caractéristiques de l'utilisateur, compatibles avec les standards existants, permettant le passage de l'apprenant d'un environnement à un autre. (iii) d'une adaptation à la fois individuelle et sociale. Pour cela, le modèle de Lausanne propose : (i) d'utiliser ISO/MLR (Metadata for Learning Resources) comme formalisme de description. (ii) de décrire le modèle d'utilisateur avec XUN1 (eXtended User Model), notre proposition d'un modèle compatible avec les standards IEEE/PAPI et IMS/LIP. (iii) d'adapter l'algorithme des fourmis au contexte de l'apprentissage à distance afin de générer des parcours personnalisés. La dimension individuelle est aussi prise en compte par la mise en correspondance de MLR et de XUM. Pour valider notre modèle, nous avons développé une application et testé plusieurs scenarii mettant en action des utilisateurs différents à des moments différents. Nous avons ensuite procédé à des comparaisons entre ce que retourne le système et ce que suggère l'expert. Les résultats s'étant avérés satisfaisants dans la mesure où à chaque fois le système retourne un parcours semblable à celui qu'aurait proposé l'expert, nous sommes confortées dans notre approche.

Small bowel bacterial overgrowth is found in 71% of IBS patients and associated symptoms respond well to Rifaximin in a phase IV trial

Background a nd A ims: The prevalence of small intestinal bowel bacterial o vergrowth (SIBO) i n patients w ith irritable bowel syndrome (IBS) ranges from 43% to 78% as determined by t he lactulose hydrogen breath (LHBT) t est. Although rifaximine, a non-absorbable antibiotic, h as b een able to decrease I BS s ymptoms i n placebo-controlled r andomized trials, these results were not repeated in phase IV studies. We aimed to assess the prevalence of SIBO in an IBS cohort and to evaluate the response to rifaximin. Methods: I BS p atients f ulfilled Rome III criteria, had an absence of alarm symptoms, n ormal f ecal c alproectin, and normal e ndoscopic workup. They underwent lactulose hydrogen breath t esting (LHBT) for SIBO diagnosis. P atients with SIBO were t reated w ith rifaximine tablets f or 14 d ays. Symptoms were a ssessed by q uestionnaires before rifaximin treatment and at week 6. Results: Hundred-fifty IBS patients were enrolled (76% female, mean age 44 ± 16 years), of whom 106 (71%) were diagnosed with SIBO and consequently treated with rifaximine. Rifaximine treatment s ignificantly reduced the following symptoms as assessed by t he s ymptom q uestionnaire: bloating (5.5 ± 2.6 before vs. 3 .6 ± 2.7 after treatment, p <0.001), flatulence (5 ± 2.7 vs. 4 ± 2.7, p = 0.015), diarrhea (2.9 ± 2.4 vs. 2 ± 2.4, p = 0.005), abdominal pain (4.8 ± 2.7 vs. 3.3 ± 2.5, p <0.001) and resulted in improved overall well-being (3.9 ± 2.4 vs. 2.7 ± 2.3, p <0.001). The LHBT was repeated 2-4 weeks after rifaximine treatment in 6 5/93 (70%) patients. Eradication of SIBO was documented in 85% of all patients (55/65). Conclusions: The results o f our phase IV trial i ndicate that a high proportion of IBS p atients t ested positive f or SIBO. I BS symptoms w ere significantly diminished following a 2-week treatment with rifaximine.

Estudio sobre la interoperabilidad de Moodle con herramientas externas

Se describe en este proyecto la necesidad de integración de herramientas en un Learning Management System (LMS), en nuestro caso Moodle, para mejorar la colaboración, reforzar y ampliar conocimiento, así como facilitar el desarrollo de la actividad docente al estar todas las herramientas centralizadas. Se realizará una comparación entre la utilización de servicios web, un framework y el estándar IMS-LTI.

QuesTInSitu: from tests to routes for assessment in situ activities

Test-based assessment tools are mostly focused on the use of computers. However, advanced Information and Communication Technologies, such as handheld devices, opens up the possibilities of creating new assessment scenarios, increasing the teachers’ choices to design more appropriate tests for their subject areas. In this paper we use the term Computing-Based Testing (CBT) instead of Computer-Based Testing, as it captures better the emerging trends. Within the CBT context, the paper is centred on proposing an approach for “Assessment in situ” activities, where questions have to be answered in front of a real space/location (situ). In particular, we present the QuesTInSitu software implementation that includes both an editor and a player based on the IMS Question and Test Interoperability specification and GoogleMaps. With QuesTInSitu teachers can create geolocated questions and tests (routes), and students can answer the tests using mobile devices with GPS when following a route. Three illustrating scenarios and the results from the implementation of one of them in a real educational situation show that QuesTInSitu enables the creation of innovative, enriched and context-aware assessment activities. The results also indicate that the use of mobile devices and location-based systems in assessment activities facilitates students to put explorative and spatial skills into practice and fosters their motivation, reflection and personal observation.

Collage, a Collaborative Learning Design Editor Based on Patterns

This paper introduces Collage, a high-level IMS-LD compliant authoring tool that is specialized for CSCL (Computer-Supported Collaborative Learning). Nowadays CSCL is a key trend in elearning since it highlights the importance of social interactions as an essential element of learning. CSCL is an interdisciplinary domain, which demands participatory design techniques that allow teachers to get directly involved in design activities. Developing CSCL designs using LD is a difficult task for teachers since LD is a complex technical specification and modelling collaborative characteristics can be tricky. Collage helps teachers in the process of creating their own potentially effective collaborative Learning Designs by reusing and customizing patterns, according to the requirements of a particular learning situation. These patterns, called Collaborative Learning Flow Patterns (CLFPs), represent best practices that are repetitively used by practitioners when structuring the flow of (collaborative) learning activities. An example of an LD that can be created using Collage is illustrated in the paper. Preliminary evaluation results show that teachers, with experience in CL but without LD knowledge, can successfully design real collaborative learning experiences using Collage.

A multicase study for the evaluation of a pattern-based visual design process for collaborative learning

Collage is a pattern-based visual design authoring tool for the creation of collaborative learning scripts computationally modelled with IMS Learning Design (LD). The pattern-based visual approach aims to provide teachers with design ideas that are based on broadly accepted practices. Besides, it seeks hiding the LD notation so that teachers can easily create their own designs. The use of visual representations supports both the understanding of the design ideas and the usability of the authoring tool. This paper presents a multicase study comprising three different cases that evaluate the approach from different perspectives. The first case includes workshops where teachers use Collage. A second case implies the design of a scenario proposed by a third-party using related approaches. The third case analyzes a situation where students follow a design created with Collage. The cross-case analysis provides a global understanding of the possibilities and limitations of the pattern-based visual design approach.

Free-and open source software for a course on network management: authoring and enactment of scripts based on collaborative learning strategies

This paper describes a Computer-Supported Collaborative Learning (CSCL) case study in engineering education carried out within the context of a network management course. The case study shows that the use of two computing tools developed by the authors and based on Free- and Open-Source Software (FOSS) provide significant educational benefits over traditional engineering pedagogical approaches in terms of both concepts and engineering competencies acquisition. First, the Collage authoring tool guides and supports the course teacher in the process of authoring computer-interpretable representations (using the IMS Learning Design standard notation) of effective collaborative pedagogical designs. Besides, the Gridcole system supports the enactment of that design by guiding the students throughout the prescribed sequence of learning activities. The paper introduces the goals and context of the case study, elaborates onhow Collage and Gridcole were employed, describes the applied evaluation methodology, anddiscusses the most significant findings derived from the case study.

CLFP intrinsic constraints-based group management of blended learning situations

When applying a Collaborative Learning Flow Pattern (CLFP) to structure sequences of activities in real contexts, one of the tasks is to organize groups of students according to the constraints imposed by the pattern. Sometimes,unexpected events occurring at runtime force this pre-defined distribution to be changed. In such situations, an adjustment of the group structures to be adapted to the new context is needed. If the collaborative pattern is complex, this group redefinitionmight be difficult and time consuming to be carried out in real time. In this context, technology can help on notifying the teacher which incompatibilitiesbetween the actual context and the constraints imposed by the pattern. This chapter presents a flexible solution for supporting teachers in the group organization profiting from the intrinsic constraints defined by a CLFPs codified in IMS Learning Design. A prototype of a web-based tool for the TAPPS and Jigsaw CLFPs and the preliminary results of a controlled user study are alsopresented as a first step towards flexible technological systems to support grouping tasks in this context.

Diseño, implementación y evaluación de un juego pervasivo basado en puzles dentro del edificio Tànger (UPF)

Las nuevas generaciones de estudiantes se caracterizan en que han crecido inmersas en la tecnología digital, hecho que ha cambiado sus costumbres y preferencias en la forma de estudiar. Así que es necesario ingeniar nuevas técnicas de aprendizaje y buscar un complemento al poco atractivo y desmotivador material físico tradicional. Una de las alternativas que se plantean es utilizar juegos educativos como herramienta de aprendizaje, aportándonos innovación, motivación y un aprendizaje activo que no nos aportan técnicas más tradicionales.Esta metodología basada en el uso de juegos educativos puede afectar positivamente en un campo de educación perjudicado como es el área de las ingenierías del área de Tecnologías de la Información y la Comunicación (TIC), donde cada vez son más los jóvenes que deciden no estudiar carreras técnicas. Ante esta situación, aplicar juegos educativos puede ser una buena solución. Este proyecto consistirá en diseñar e implementar un juego educativo enfocado a aprender sobre algunos conceptos que se tratan en los grados de ingeniería informática, telemática y sistemas audiovisuales de la Universidad Pompeu Fabra (UPF). En concreto, el juego que se ha diseñado e implementado se caracteriza por seguir un modelo conceptual que define qué elementos han de contener un tipo concreto de juegos basados en puzles. Además, aprovechando las ventajas que aportan los estándares educativos, utilizaremos la especificación de IMS Learning Design, como parte de la implementación del juego. Por otro lado, nuestro juego será diseñado para dispositivos móviles y, por consiguiente, consistirá en un juego pervasivo en el que los estudiantes se tendrán que mover por el edificio Tànger de la UPF para poder resolver los diferentes problemas planteados. Finalmente, el juego será evaluado con diferentes estudiantes y serán analizados sus resultados para extraer las conclusiones oportunas.

Diseño, implementación y evaluación de un juego basado en puzzles para el aprendizaje de redes de ordenadores

El aprendizaje basado en juegos proporciona a los alumnos una forma de aprender más motivadora y gratificante al estudiante. Los juegos educativos permiten a los estudiantes centrarse completamente en un contenido concreto, resultándoles beneficioso a la hora de profundizar su conocimiento en esa materia. Esta forma de educar puede ayudar a revertir la situación actual de desinterés de los alumnos por las asignaturas del área de las ingenierías de las Tecnologías de la Información y la Comunicación (TIC). En este sentido, estudios realizados y estadísticas demuestran que las matriculaciones en este sector han disminuido en los últimos años. Teniendo en cuenta estos factores, en este PFC se ha diseñado un juego educativo, basado en puzzles, para aprender conceptos relacionados con las redes de ordenadores, una de las temáticas principales en el campo de las ingenierías TIC. El diseño del juego está fundamentado en un modelo conceptual que define los elementos necesarios para crear juegos basados en puzzles. Por otra parte, en este PFC se hace uso de estándares educativos (en concreto, de la especificación de IMS Learning Design), para la implementación del juego. De este modo, el juego se beneficia de las ventajas derivadas del uso de estándares educativos: definición, compartición y reutilización de objetos de aprendizaje para el diseño, intercambio y la reutilización de estrategias pedagógicas, facilitando la interoperabilidad de los diseños pedagógicos complejos. Además, el juego se ha implementado con tecnología para Android,pudiendo de esta manera ser utilizado en dispositivos móviles que utilicen esta tecnología. Por último, nuestro juego ha sido evaluado por estudiantes de un centro escolar con el fin de analizar los resultados obtenidos a partir de sus opiniones y valoraciones.

Herramienta de autoría para la creación de juegos basados en puzles

L'aprenentatge basat en jocs facilita el millor enteniment de conceptes, aportant entorns estimulants on poder aprendre d'una manera diferent a l'actual. Alguns dels avantatges més destacables són, per exemple, que els jocs fomenten la capacitat dels jugadors per comunicar-se i interactuar entre si. D'altra banda també poden ajudar a pensar de manera critica quan tenenque establir vincles entre la vida virtual i la real, estimulant-los a intentar trobar la solució diferents maneres. Malgrat això, hi ha una escassetat d'eines que permetin als professors poder crear els seus propis jocs educatius.Per donar solució a aquest problema s'ha dissenyat un model conceptual que defineix els elements necessaris perquè professors puguin dissenyar els seus propis jocs educatius basats en puzles. En aquest PFC ens centrarem en el disseny i implementació d'una eina d'autoria que generi els documents d'acord amb aquest model conceptual. En concret, aquesta eina d'autorias'encarregarà de demanar la informació necessària per poder realitzar la creació del joc, de manera que qualsevol persona que tingui o no habilitats de programació, tingui una petita eina que li guiï pas a pas i li generi els arxius necessaris per a la creació d'aquests jocs. D'altra banda, donada els avantatges de l'ús d'estàndards educatius en sistemes d'e-learning, destacar queaquesta eina d'autoria és conforme a l'especificació d'IMS Learning Design (IMS LD). És per això que, com a resultat, l'eina s'encarrega d'emmagatzemar la informació necessària per després processar-la i generar els arxius corresponents a IMS LD per definir el flux d'activitats dels jocs, i els arxius corresponents al model conceptual que defineix els mecanismes de comportamentdels puzles associats a les activitats.

The determinants of pricing in pharmaceuticals: Are U.S. prices really higher than those of Canada?

This paper studies price determination in pharmaceutical markets using data for 25 countries, six years and a comprehensive list of products from the MIDAS IMS database. We show that market power and the quality of the product has a significantly positive impact of prices. The nationality of the producer appears to have a small and often insignificant impact on prices, which suggests that countries which regulates prices have relatively little power to do it in a way that advances narrow national interest. We produce a theoretical explanation for this phenomenon based on the fact that low negotiated prices in a country would have a knock-on effect in other markets, and is thus strongly resisted by producers.Another key finding is that the U.S. has prices that are not significantly higher than those of countries with similar income levels. This, together with the former observation on the effect of the nationality of producers casts doubt on the ability of countries to pursue "free-riding" regulation.